Metam S9dium/Metam <:>tassi~m!MITC ~~~istrat~on Review Hun:~n-::_Health Asse~sment Scopi~g J?~~ument 

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY 

WASHINGTON, D.C. 20460 

OFFICE OF 

CHEMICAL SAFETY AND 

POLLUTION PREVENTION 

MEMORANDUM 

Date: September 4, 2013 

SUBJECT: Metam Sodium, Metam Potassium, and MITC. Human-Health Assessment 

Seeping Document in Support of Registration Review. 

PC Code: Metam Sodium PC Code: 039003, Metam 

Potassium PC Code: 039002, MITC PC Code: 068103 

Decision No.: '/7Sf?lf2 

DP Barcode: D409657 

Registration No.: N/A 

Petition No.: N/A Regulatory Action: Registration Review Scoping 

Document 

Risk Assessment Type: N/ A 

TXR No.: N/A 

Case No.: 2390 

CAS No.: Metam Sodium: 6734-80-1, Metam Potassium: 

137-41-7, MITC: 556-61-6 

MRID No.: N/A 

FROM: 

40CFR: N/A 

Shalu Shelat, Industrial Hygienist ~ ~ "'\.[Y-l\.3 

Nancy McCarroll, Toxicologist jff_~f11"'£J 1 ~~~I) Christopher Schlosser, Toxicologist......:::;;~~:<::::----

Risk Assessment Branch 6 (RABV ) 

~:aries Smith, Branch C.hief. ~ ?-/ (' ">)-~ Risk Assessment Branch 1 (RA<i3~<: z_ .. / 

Health Effects Division (7509P) -/ 

Nathan Mottl, Biologist /J~Mll? 1 

/'Cit/', 

Risk Assessment and Science Support Branch 

Antimicrobials Division (751 OP) 

THROUGH: Felecia Fort, Branch Chief :;( r I I 

Risk Assessment Branch 6 (RABV 1 ~ u oJ(t\..:+ <t ~ ) 3 

Health Effects Division (7509P) [) . . r J 

Steve Weiss, Branch · e ~~~ S ~Ale~_) f / S 1 /3 

Tim Leighton, Senior ~ ~ Tk~ 9/ s-Its 

Risk Assessment and Sci e upport ranch -- J 

Antimicrobials Division (751 OP) 

TO: Jose Gayoso, Chemical Review Manager 

Risk Management and Implementation Branch II 

Pesticide Re-Evaluation Division (7508P) 

Attached is the combined HED and AD human-health risk assessment seeping document for 

metam sodium; metarn potassium, and MITC to support registration review. 

Page 1 of27 
Metam Sodium/Metam Potass U_!!l MI~~ ~e~istr~!i?? Re~i~~}-lu!D_~_n-I:Iealth __ ~~sessment Scoping Document 

Executive Summary 

Metam sodium (sodium N-methyldithiocarbamate) and metam potassium (potassium Nmethyldithiocarbamate) are non-selective pre-plant soil fumigants with fungicidal, herbicidal, 

insecticidal, and nematicidal properties. The primary degradate for both metam sodium and 

metam potassium is methyl isothiocyanate (MITC). Metam sodium, metam potassium, and 

MITC also are active ingredients in a variety of antimicrobial products. The Health Effects 

Division (HED) and the Antimicrobial Division (AD) have evaluated the status of the humanhealth assessments for metam sodium, metam potassium, and MITC to determine whether 

sufficient data are available to support Registration Review. HED and AD have also considered 

the most recent human-health risk assessments for metam sodium, metam potassium, and MITC 

with respect to toxicity, exposure, and usage databases, and the most updated Agency science 

policy and risk assessment methodologies to determine the scope of work necessary to support 

Registration Review. It is noted that dazomet is another pesticide that produces MITC upon 

application, however this document does not include exposure to dazomet or MITC resulting 

from dazomet applications. 

The Amended Metam Sodium/Potassium and MITC Reregistration Eligibility Decision (RED) 

document was issued in May 2009. The Amended RED focused on four basic metam 

sodium/potassium application categories, including: (I) use as an agricultural soil fumigant for 

food, feed, and fiber crops; (2) use on golf course turf and for application to small areas of turf 

and soil; (3) use as a root-control agent in drains and sewers; and (4) use ofmetam potassium as 

an antimicrobial for pulp and paper, recirculating cooling towers, and industrial water 

purification systems and use of metam sodium as an antimicrobial for remedial treatment of 

wood poles and treatment of sewage sludge and animal waste (only supported by one registrant). 

The Amended RED detailed a number of letters that the Agency received requesting the 

voluntary cancellation of several of the metam sodium and metam potassium antimicrobial uses. 

On August 20, 2008, the Agency published a Section 6 (f) notice in the Federal Register 

(Federal Register Notice Vol. 73, No. 162) to delete the uses specified in the RED from labels. 

The Agency is in the process of amending these labels to remove all of the canceled uses. 

Additionally, the Amended RED also included MITC use as an antimicrobial agent for remedial 

wood treatment. No new uses of these three active ingredients have been registered since the 

Amended RED was issued. 

The toxicity database for metam sodium and metam potassium is adequate for Registration 

Review with the exception of an MITC reproduction and fertility effects study and the 

chronic/carcinogenicity studies. These studies were required as part of the 2009 Amended RED 

and are currently being performed. The registrants have completed and submitted a number of 

other MITC toxicity studies required as part of the 2009 Amended RED including an acute study 

via the inhalation route, a developmental toxicity screening test via the inhalation route, an 

unscheduled DNA synthesis in mammalian cells in culture study, and an Immunotoxicity study 

via the inhalation route. The Agency will review and incorporate all of these studies during 

Registration Review. The focal points for the assessment of metam sodium, metam potassium 

and MITC are occupational dermal exposure to metam sodium and metam potassium and 

occupational and residential inhalation exposure to MITC. There is no route specific dermal 

study available for metam sodium/potassium however a metam sodium rat dermal absorption 

study is available (dermal absorption of2.5%). There are a number of route specific MITC 

inhalation studies available including an acute inhalation neurotoxicity study in rats, a 28-day 

inhalation study in rats, and a 13-week inhalation study in rats. There is also an eye irritation and 

odor threshold study performed with human subjects that indicates the irritation properties of 

Page 2 of27 
Metam Sodium/Metam Potassium/MITC Registration Review Human-Health Assessment Scoping Document

_____________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________ __________________________

Page 3 of 27

MITC. During Registration Review, the Agency will reevaluate the points of departure (PODs)

and uncertainty factors (UFs) for the residential and occupational exposure assessments.

The residue chemistry and dietary-exposure databases are adequate to support current 

registration requirements. The current uses of metam sodium and metam potassium have 

previously been determined to be non-food uses. In addition, based on environmental fate data, 

the residual contents in soils, and monitoring data, MITC is not expected to adversely impact the 

drinking water sources such as surface water and ground water. Dietary and drinking water 

assessments are not anticipated during Registration Review.

The occupational and residential exposure database for metam sodium, metam potassium, and 

MITC is adequate for Registration Review with the exception of an ambient air study measuring 

MITC from soil fumigant applications and a number of antimicrobial occupational handler and 

post-application exposure studies required in the 2009 Amended RED. In addition, as part of 

Registration Review, the Agency requests that a shank injection tarped, bedded application flux 

study be completed (835.8100). A sewer treatment occupational exposure study (MRID 

48914201) required as part of the 2009 Amended RED was submitted and recently reviewed by 

the Agency (S. Shelat, D406497, 9/4/2013). The registrants have also completed and submitted 

a field volatility study for center pivot applications (conventional soil fumigation use) required 

for metam sodium as part of the 2009 Amended RED. The Agency will review and incorporate 

this study during Registration Review.

The Agency anticipates conducting the following risk assessment updates during Registration 

Review:

Toxicology: 

o Reevaluation of the toxicity endpoint/dose selection may be necessary based on 

the recently submitted toxicological data.

Residue Chemistry: None

Dietary Exposure: None

Occupational/Residential Exposure:

o Revised HED and AD occupational handler risk assessments may be necessary

based on the most recent exposure data, Agency policies, or if the toxicological 

reevaluation results in changes to the endpoints.

o Revised AD occupational post-application risk assessments may be necessary 

based on the most recent exposure data, Agency policies, or if the toxicological 

reevaluation results in changes to the endpoints.

o Additional or revised HED residential bystander risk assessments may be 

necessary based on the most recent exposure data, Agency policies, or if the 

toxicological reevaluation of results in changes to the endpoints.
Metam Sodium/Metam Potassium/MITC Registration Review Human-Health Assessment Scoping Document

_____________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________ __________________________

Page 4 of 27

1.0 Introduction

Metam sodium (sodium N-methyldithiocarbamate) and metam potassium (potassium Nmethyldithiocarbamate) are non-selective pre-plant soil fumigants with fungicidal, herbicidal, 

insecticidal, and nematicidal properties. When metam-sodium and metam-potassium are applied 

and mixed with moist soil or water, they are quickly broken down into several strong irritant 

products. One of these products is methyl isothiocyanate (MITC), which accounts for most of 

the fumigant activity. Metam sodium, metam potassium, and MITC also are active ingredients 

in a variety of antimicrobial products. The Health Effects Division (HED) and the Antimicrobial 

Division (AD) have evaluated the status of the human-health assessments for metam sodium, 

metam potassium, and MITC to determine whether sufficient data are available to support 

Registration Review. HED and AD have also considered the most recent human-health risk 

assessments for metam sodium, metam potassium, and MITC with respect to toxicity, exposure, 

and usage databases, and the most updated Agency science policy and risk assessment 

methodologies to determine the scope of work necessary to support Registration Review. 

Dazomet is another pesticide that produces MITC upon application however; this document does 

not include exposure to dazomet or MITC resulting from dazomet applications.

The Amended Metam Sodium/Potassium and MITC Reregistration Eligibility Decision (RED) 

document was issued in May 2009. The RED focused on four basic metam sodium/potassium 

application categories, including: (1) use as an agricultural soil fumigant for food,

feed, and fiber crops; (2) use on golf course turf and for application to small areas of turf and

soil; (3) use as a root-control agent in drains and sewers; and (4) use for a number of

antimicrobial uses listed for metam potassium (tanning drum leather, pulp and paper, 

recirculating cooling towers, and industrial water purification systems) and metam sodium 

(remedial treatment of wood poles and treatment of sewage sludge and animal waste). The RED 

also included MITC use as an antimicrobial agent for remedial wood treatment. No new uses of 

these three chemicals have been registered since the RED was issued.

The Amended RED detailed a number of letters that the Agency received requesting the 

voluntary cancellation of several of the metam sodium and metam potassium antimicrobial uses. 

The antimicrobial uses of metam-sodium that were requested for voluntary cancellation included 

(1) treatment of process waters during the production of sugar (i.e., raw cane and beet sugars), 

(2) treatment of brine-cured hides and skins (i.e., leather) during processing, and (3) treatment of 

sewage sludge and animal waste (one registrant continues to support this use, while another 

canceled this use). The antimicrobial uses of metam potassium that were requested for voluntary 

cancellation included: (1) sugar beet and cane uses; (2) all leather uses, with the exception of the 

tanning drum leather use; (3) all paint uses (including the preservation of protective colloids and 

emulsion resins); (4) all water-based drilling, completion, and packer fluid uses; (5) all 

petroleum secondary recovery operation uses; (6) all once-through cooling water applications; 

and (7) all cutting fluids (metal working fluids) uses. As a result of these cancellation letters 

these uses were not evaluated in the Amended RED and will not be evaluated in Registration 

Review. 

Subsequently, on August 20, 2008, the Agency published a Section 6 (f) notice in the Federal 

Register (Federal Register Notice Vol. 73, No. 162) to delete the uses specified in the Amended 

RED from labels. The Agency is in the process of amending these labels to remove all of the 

canceled uses. AD notes that many of the voluntarily cancelled uses of metam potassium still 

remain on current metam potassium labels. These uses include the treatment of leather; 

petroleum secondary recovery operation uses; water based drilling, completion, and packer fluid 
Metam Sodium/Metam Potassium/MITC Registration Review Human-Health Assessment Scoping Document

_____________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________ __________________________

Page 5 of 27

uses; and once-through cooling water applications. AD will be following up with the registrants 

of metam potassium on the voluntary cancelation of these remaining uses.

2.0 Hazard Identification/Toxicology

The 2009 Amended RED required a number of MITC toxicity studies, including the following: 

a neurotoxicity battery via the inhalation route (870.6200), 

a developmental toxicity screening test via the inhalation route (870.3550),

a reproduction and fertility effects study via the inhalation route (870.3800),

an unscheduled DNA synthesis in mammalian cells in culture study (870.5550),

an Immunotoxicity study via the inhalation route (870.7800),

a chronic/carcinogenicity rat study via the inhalation route (870.4200), and 

a chronic/carcinogenicity mouse study via the inhalation route (870.4200).

The registrants have completed and submitted the neurotoxicity study, the developmental study, 

the unscheduled DNA synthesis, and the Immunotoxicity study and the Agency will review and 

incorporate these studies during Registration Review. The Agency has not received the 

reproduction and fertility effects study or the chronic/carcinogenicity studies at this time. Once 

these studies are completed and submitted they will also be reviewed and incorporated during 

Registration Review.

Attachment 2 provides a summary of the acute, subchronic, and chronic toxicity profile for 

metam sodium/potassium and MITC. The relevant data from the recently submitted studies has

been incorporated into the toxicity profile. Attachment 2 provides a summary of the relevant 

toxicological endpoints used in metam sodium/potassium and MITC 2009 risk assessment. 

During Registration Review, the Agency will reevaluate the MITC endpoints, points of departure 

(PODs), and uncertainty factors (UFs) for the residential and occupational exposure assessments 

based on current HED policy, recently submitted studies, and any other outstanding data.

No inhalation pharmacokinetic or metabolism studies are available at this time for metam 

sodium/potassium or MITC. Metam sodium and metam potassium are efficiently converted to 

MITC in vivo. Oral pharmacokinetic and metabolism studies in rats are available for metam 

sodium and MITC. In those studies, metam sodium and MITC were excreted mainly in urine 

with small amounts excreted in feces. Three different compounds (MITC, carbon dioxide [CO2], 

carbon oxide sulfide [COS]/carbon disulfide [CS2]) were found to be excreted in the lungs over a 

73 hour collection period. Although the tissue with the highest uptake for all three compounds 

was the thyroid gland, it is notable that tissue retention of radioactive material was low in both 

sexes and at all doses. High uptake was also seen in the studies by the liver, kidneys, and lung, 

with the lowest level in testes, brain and eyes. Metabolic profiles detected in urine, liver, and the

kidneys were similar for metam sodium and MITC but there were some differences, mainly 

quantitative in nature. The consistent results seen in the metam sodium and MITC oral 

pharmacokinetic and metabolism studies are further supported by the similarity in the oral doses 

causing similar toxic effects for metam sodium and MITC in the available oral toxicity studies. 

Specifically, reduced body weight gain and food consumption in addition to changes in 

hematological parameters were observed at low doses in oral toxicity studies with rats, mice, 

rabbits, and dogs.

In oral developmental toxicity studies with metam sodium and MITC, effects such as fetal 

weight decrements, reduced ossification of various skeletal structures, and increased incidence of 

resorptions have been noted at similar molar dose levels. There is no quantitative susceptibility 
Metam Sodium/Metam Potassium/MITC Registration Review Human-Health Assessment Scoping Document

_____________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________ __________________________

Page 6 of 27

observed in the oral developmental and reproductive toxicity studies with metam sodium and 

MITC. All of the developmental NOAELs are equal to or larger than the NOAELs for maternal 

toxicity. There is, however, qualitative susceptibility in two rat developmental toxicity studies 

with metam sodium where increased incidence of resorptions were noted at a dose that resulted 

in maternal body weight gain decreases. 

The focal points for the assessment of metam sodium, metam potassium and MITC are dermal 

exposure to metam sodium and metam potassium and the inhalation exposure to MITC. There is 

no route specific dermal study available for metam sodium/potassium however a metam sodium 

rat dermal absorption study is available (dermal absorption of 2.5%). There are a number of 

route specific MITC inhalation studies available including an acute inhalation neurotoxicity 

study in rats, a 28-day inhalation study in rats, and a 13-week inhalation study in rats. There is 

also an eye irritation and odor threshold study performed with human subjects that indicates the 

irritation properties of MITC.

Metam sodium/potassium are classified as a probable human carcinogens based on statistically 

significant increases in malignant angiosarcomas in both sexes of the CD-1 mouse in male. For 

the purpose of risk characterization, a low dose extrapolation model was applied to the animal 

data for the quantification of human risk (Q1*), based on the total incidence of angiosarcomas in 

male mice at all sites combined (Q1* = 1.98x10-1). For MITC, there are currently insufficient 

data to characterize the cancer risk of MITC. As mentioned above, chronic/carcinogenicity 

studies for MITC were required as part of the 2009 Amended RED. HED will reevaluate the 

carcinogenic potential of MITC during Registration Review after these studies are submitted and 

reviewed.

Conclusions: The toxicity databases for metam sodium/potassium and MITC are adequate for 

Registration Review except for the outstanding toxicity studies (i.e., the reproduction and 

fertility effects study and the chronic/carcinogenicity studies) required in the 2009 Amended 

RED. During Registration Review, the Agency will reevaluate the points of departure (PODs) 

and uncertainty factors (UFs) for the residential and occupational exposure assessments based on 

current HED policy, recently submitted studies, and any other outstanding data.

3.0 Residue Chemistry

The residue chemistry databases for metam sodium/potassium and MITC are adequate for 

Registration Review. The Agency previously decided that there is no reasonable expectation of 

finite residues to be incurred in/on food and feed crops when metam sodium and metam

potassium are used as preplant soil fumigants, so these uses are considered non-food uses, and 

tolerances are not needed (Kinard; D293347; 9/30/2003). There is also no reasonable 

expectation of finite residues in/on food for the antimicrobial uses of metam sodium/potassium

and MITC.

Conclusions: The residue chemistry databases for metam sodium/potassium and MITC are 

adequate for Registration Review. 

4.0 Dietary Exposure

The dietary exposure databases for metam sodium/potassium and MITC are adequate for 

Registration Review. As described in Section 3.0, the Agency previously decided that there is no 
Metam Sodium/Metam Potassium/MITC Registration Review Human-Health Assessment Scoping Document

_____________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________ __________________________

Page 7 of 27

reasonable expectation of finite residues to be incurred in/on food and feed crops based on the 

currently registered uses of metam sodium and metam potassium.

Environmental fate data suggest that there is a low potential for the parent compound metam 

sodium or metam potassium to be present in drinking water due to the rapid degradation of 

metam sodium/potassium to MITC in the environment. MITC could potentially move to surface 

water through runoff under an intense rainfall and/or if continuous irrigation occurs right after 

metam sodium application. However, the Henry’s Law Constant of 1.79 x 10-4 atm-m

3

/mol for 

MITC suggests that it would volatilize quickly from surface water. In addition, under most field 

conditions, the potential for significant ground water contamination of MITC is unlikely due to 

its volatilization and fast degradation in soil. MITC was not detected in any available nontargeted ground water monitoring samples within the USA. Based on environmental fate data, 

the residual contents in soils, and monitoring data, the Agency does not expect MITC to 

adversely impact the drinking water sources such as surface water and ground water.

Based on the discussion above, no dietary or drinking water assessments have been previously 

performed for metam sodium, metam potassium, or MITC.

Conclusions: The dietary exposure databases for metam sodium/potassium and MITC are 

adequate for Registration Review. Dietary and drinking water assessments are not anticipated

during Registration Review.

5.0 Residential Exposure

The 2009 Amended RED required two MITC residential exposure studies for the conventional 

uses of metam sodium/potassium, including the following: 

a field volatility study for center pivot applications of metam sodium/potassium 

(835.8100), and 

an ambient air monitoring study for MITC (non-guideline).

The registrants have completed and submitted the center pivot field volatility study and the

Agency will review and incorporate this study during Registration Review. The Agency has not 

received the ambient air monitoring study at this time. Once this study is completed and

submitted, it will also be reviewed and incorporated during Registration Review. In addition, the 

Agency requests that a shank injection tarped, bedded application flux study be completed

(835.8100). Previously submitted tarped, bedded flux studies did not utilize a true shank 

injection application rig and consequently these studies may not accurately reflect potential 

bystander inhalation exposures. Such a study should include multiple fields and multiple tarps, 

one of which should be a standard LDPE tarp. 

There are currently no registered residential uses of metam sodium/potassium or MITC. 

However, there is the potential for residential bystander inhalation exposure to MITC after a soil 

fumigation application of metam sodium or metam potassium. The Agency has specifically

focused on assessing acute MITC inhalation exposures resulting from metam sodium/potassium

applications because peak MITC air concentrations typically occur in the first 24 or 48 hours 

after application. There is also the potential for inhalation exposure to MITC via ambient air. 

These exposures can be acute as well as longer-term in nature. 

There are two recent documents that analyzed acute residential bystander inhalation exposure to 

MITC based on numerous field volatility studies and PERFUM (Probabilistic Exposure and Risk 

model for Fumigants) air modeling for a variety of metam sodium/potassium applications 
Metam Sodium/Metam Potassium/MITC Registration Review Human-Health Assessment Scoping Document

_____________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________ __________________________

Page 8 of 27

(Smith; D357118; 8/30/2009 and Shelat and Smith; D385289; 1/06/2011). The results of these 

assessments show that bystander inhalation exposure to MITC after a soil fumigation application 

of metam sodium/potassium can vary depending on a variety of factors such as application 

method, agricultural tarps, water seals, and a number of soil parameters (i.e., soil moisture, 

organic content, etc.). For many application scenarios, the PERFUM air modeling results 

showed that acceptable MITC air concentrations were attainable at some distance from a treated 

field and thus buffer zones were required to protect residential bystanders. The 2009 Amended 

Reregistration Eligibility Decision (RED) Document for Methyldithiocarbamate Salts (Metamsodium, Metam-potassium) and Methyl Isothiocyanate (MITC) provides more information on 

buffer zone development.

There are two recent documents that analyzed ambient air inhalation exposure to MITC based on 

numerous ambient air monitoring studies from California and Washington (Smith; D357118; 

8/30/2009 and Shelat; D406930; 2/26/2013). The results of these assessments show that ambient 

air inhalation exposures to MITC can occur for extended periods especially in areas of high use 

during the season of high use. In some cases, acute as well as short- and intermediate-term risks 

exceed HED’s level of concern for MITC (MOEs < 10 for acute and MOEs < 30 for short- and 

intermediate-term).

Conclusions: 

The residential exposure databases for metam sodium/potassium and MITC are adequate for 

Registration Review except for the outstanding exposure study (i.e., the ambient air study) 

required in the 2009 Amended RED. In addition, as part of Registration Review, the Agency 

requests that a shank injection tarped, bedded application flux study be completed. HED will 

review and incorporate all of these studies during Registration Review. Additional or updated 

PERFUM modeling and ambient air analyses may be required during Registration Review if the 

points of departure (PODs) or uncertainty factors (UFs) for the residential exposure assessment

change based on the toxicological data required as part of the 2009 Amended RED.

During Registration Review, HED also plans to update the fumigant factors document (Dawson, 

Smith, and Shelat; D385314; 1/11/2011). The fumigant factors document provides a discussion 

of values and parameters used as the basis for buffer reduction credits (i.e., tarps) as well as for 

establishing GAPs (i.e., soil moisture) for the fumigants. This document impacts all of the soil 

fumigants including metam sodium/potassium and MITC.

6.0 Aggregate-Risk Assessment

Acute and chronic aggregate-risk assessments were not previously performed for metam sodium, 

metam potassium, or MITC because no dietary and drinking water assessments were performed

(see Section 3.0 and 4.0 above).

Conclusions: 

Acute and chronic aggregate risk assessments are not anticipated during Registration Review.

7.0 Occupational Exposure

The 2009 Amended RED required one MITC occupational exposure study for the conventional 

sewer use of metam sodium. The registrants have submitted this study (MRID 48914201) and

based on HED’s review (D406497), the updated MITC occupational handler inhalation risk 
Metam Sodium/Metam Potassium/MITC Registration Review Human-Health Assessment Scoping Document

_____________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________ __________________________

Page 9 of 27

estimates for the metam sodium sewer use are all below HED’s level of concern (i.e., MOEs ≥ 

10 for acute scenarios and MOEs ≥ 30 for short-term scenarios).

The 2009 Amended RED required the following occupational exposure studies for the 

antimicrobial uses of metam sodium and metam potassium:

Metam sodium handler dermal and inhalation exposure studies for liquid pour data for 

the wood pole treatment use.

Metam sodium product use and a post-application inhalation exposure study (e.g., 

exposure to degradate MITC) for the sewage sludge and animal waste use. 

Metam Potassium product use data and a post-application inhalation exposure study (e.g. 

exposure to degradate MITC) for the cooling water tower and industrial water 

purification facility uses.

The Agency has not received these studies at this time. Upon receipt of these data, AD will 

review and incorporate these data during Registration Review.

There are four main categories of registered occupational uses of metam sodium/potassium, 

including the following: (1) use as an agricultural soil fumigant for all food, feed, and fiber 

crops; (2) use on golf course turf and for application to small areas of turf and soil; (3) use as a 

root-control agent in drains and sewers; and (4) use of metam potassium as an antimicrobial for 

pulp and paper, recirculating cooling towers, and industrial water purification systems and use 

of metam sodium as an antimicrobial for remedial treatment of wood poles and treatment of 

sewage sludge and animal waste (only supported by one registrant). MITC itself is registered as 

an antimicrobial agent for remedial wood treatment. No new uses of these three active 

ingredients have been registered since the Amended RED was issued.

Occupational Handlers

Conventional Uses

There is potential for occupational handler dermal exposure to metam sodium/potassium and 

inhalation exposure to MITC to occur based on the registered conventional uses of metam 

sodium/potassium. The most recent HED document that analyzed the potential occupational 

handler risks to metam sodium/potassium and MITC is the 2009 risk assessment (Smith; 

D357118; 8/30/2009). HED assessed the short- and intermediate-term dermal exposure and the 

cancer exposure for two major uses of metam sodium/potassium, soil fumigation and sewer 

fumigation. HED also assessed both acute and short- and intermediate-term MITC inhalation 

exposure for two major uses of metam sodium/potassium, soil fumigation and sewer fumigation.

For soil fumigation, HED utilized surrogate data from the Pesticide Handlers Exposure Database 

(PHED) and the Outdoor Residential Exposure Task Force (ORETF) to assess occupational 

handler dermal exposures to the soil fumigant uses of metam sodium/potassium in the 2009 

assessment. These assessments were considered conservative because PHED and ORETF data 

are based on non-volatile chemicals while metam sodium/potassium can quickly break down to 

MITC. In many cases, short- and intermediate-term and cancer risks exceeded HED’s level of 

concern for the soil fumigant uses of metam sodium/potassium. HED also utilized a number of 

MITC specific inhalation exposure studies to assess occupational handler inhalation exposures to 

MITC in the 2009 assessment. These MITC studies examined a variety of tasks associated with 

soil fumigation such as loading and applying. In some cases, acute as well as short- and 

intermediate-term risks exceeded HED’s level of concern for MITC at baseline (MOEs < 10 for 

acute and MOEs < 30 for short- and intermediate-term). Even with the addition of an organic 
Metam Sodium/Metam Potassium/MITC Registration Review Human-Health Assessment Scoping Document

_____________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________ __________________________

Page 10 of 27

vapor respirator, some acute as well as short- and intermediate-term risks exceeded HED’s level 

of concern for MITC.

For sewer fumigation, HED utilized surrogate data from the Pesticide Handlers Exposure 

Database (PHED) to assess occupational handler dermal exposures to the sewer fumigant use of 

metam sodium in the 2009 assessment. These assessments were considered conservative 

because PHED data are based on non-volatile chemicals while metam sodium can quickly break 

down to MITC. In many cases, short- and intermediate-term and cancer risks exceed HED’s 

level of concern for the sewer fumigant use of metam sodium. HED also utilized two Australian 

studies that measured inhalation exposure to MITC during the application of metam sodium to 

sewers to assess occupational handler inhalation exposures to MITC in the 2009 assessment. 

The Registrants have since submitted an observational occupational sewer application MITC 

inhalation exposure study. Based on the submitted study, the updated MITC occupational 

handler inhalation risk estimates for the metam sodium sewer use are all below HED’s level of 

concern (i.e., MOEs ≥ 10 for acute scenarios and MOEs ≥ 30 for short-term scenarios).

Antimicrobial Uses

Metam Sodium

There is potential for occupational handler dermal and inhalation exposure to metam sodium 

based on the registered antimicrobial uses of metam sodium. Because of the short loading and/or 

application durations (i.e., minutes), handlers are not expected to be exposed to MITC from the 

registered antimicrobial uses of metam sodium. The most recent AD document that analyzed the 

metam sodium potential occupational handler risks to metam sodium is the 2008 risk assessment 

(Leighton and Walls; D335651; 2/14/2008). 

The 2008 metam sodium occupational assessment assessed the potential non-cancer and cancer 

handler risks for the wood pole and sewage sludge uses. The sewage sludge use did not result in 

any non-cancer dermal and inhalation or cancer risks of concern. The wood pole use resulted in 

non-cancer dermal and inhalation risks to the handlers did not exceed AD’s level of concern (i.e., 

all MOEs greater than 100). The cancer risks for the handlers are in the range of 2.2E-5 to 3.4E6 for treating poles. Additional label language was required on labels to mitigate the cancer risk. 

The RED lists the following risk mitigation measures:

-Plug the pre-drilled holes immediately after applications;

-Do not treat structures/beams indoors; and

-Do not drill an application hole through seasoning checks to apply product. If the hole intersects 

an internal void or rot pocket, redrill the holes farther up the pole into relatively solid wood.

AD will reassess the handler wood pole uses in Registration Review upon receipt and review of 

the handler exposure data required in the Amended RED data.

Metam Potassium

There is potential for occupational handler dermal and inhalation exposure to metam potassium 

based on the registered antimicrobial uses of metam potassium. Because of the short loading 

and/or application durations (i.e., minutes), handlers are not expected to be exposed to MITC 

from the registered antimicrobial uses of metam potassium. The most recent AD risk assessment 

for the RED analyzed the metam potassium potential occupational handler risks is the 2008 risk 

assessment (Leighton and Walls; 2/14/2008).
Metam Sodium/Metam Potassium/MITC Registration Review Human-Health Assessment Scoping Document

_____________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________ __________________________

Page 11 of 27

The 2008 metam potassium occupational assessment assessed the potential non-cancer and 

cancer handler risks for the recirculating cooling water (closed mixing/loading scenario) and 

industrial water sewage use of metam potassium (closed mixing/loading scenario). These uses 

did not result in any non-cancer dermal and inhalation or cancer risks of concern.

MITC 

Although MITC has a high vapor pressure; based on the product formulation (solid form), 

product packaging (enclosed in an aluminum rod), application method (injected then capped), 

required PPE, and duration of handling the product the potential for MITC handler dermal or 

inhalation exposure is negligible. As a result, a quantitative risk assessment was not conducted 

for the Amended RED and is not anticipated to be needed for Registration Review. 

Occupational Post-Application

Conventional Uses

HED previously determined there were MITC inhalation risk concerns for workers reentering 

metam sodium/potassium fumigated fields 48 hours after application. As part of the 2009 

Amended RED, the Agency placed various restrictions on reentry of workers into fumigated 

fields. With these restrictions, HED believes that risks to reentry workers will not exceed the 

HED’s level of concern.

HED does not expect occupational post-application inhalation exposure to MITC to occur from 

the sewer fumigant use of metam sodium.

Antimicrobial Uses

There is potential for occupational post-application inhalation exposure to MITC from the metam 

sodium sewage sludge use and the metam potassium industrial water purification system and 

recirculating cooling tower uses. No post-application exposure is expected to result for the 

remedial wood treatment uses because the treated holes in the wood are capped/plugged and 

contact with treated poles occurs infrequently. Upon receipt of the product use data and the

MITC (from metam sodium and metam potassium uses) post-application inhalation exposure

data requested as part of the Amended RED, AD will review and incorporate these data during 

Registration Review.

Conclusions: The occupational exposure database is adequate to support the Registration 

Review process for the conventional uses of metam sodium/potassium and MITC. HED will 

review and incorporate the submitted metam sodium sewer fumigant study during Registration 

Review. HED may be required to update the occupational handler assessments during 

Registration Review if the points of departure (PODs) or uncertainty factors (UFs) for the 

occupational exposure assessment change based on the toxicological data required as part of the 

2009 Amended RED.

The occupational exposure database is adequate to support the Registration Review process for 

the antimicrobial uses of metam sodium/potassium and MITC except for the outstanding product 

use and handler and post-application exposure studies required in the 2009 Amended RED. 

Upon receipt of the requested data, AD will review and incorporate the studies during 

Registration Review. AD may be required to update the occupational handler and postapplication assessments during Registration Review if the points of departure (PODs) or 
Metam Sodium/Metam Potassium/MITC Registration Review Human-Health Assessment Scoping Document

_____________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________ __________________________

Page 12 of 27

uncertainty factors (UFs) for the occupational exposure assessment change based on the 

toxicological data required as part of the 2009 Amended RED.

8.0 Public Health and Pesticide Epidemiology Data

An updated review of metam sodium, metam potassium and MITC incident reports was recently 

prepared by HED (Recore and Evans, D414492, 08/29/2013). For this evaluation, both OPP 

Incident Data System (IDS) and the Centers for Disease Control and Prevention/National 

Institute for Occupational Safety and Health (CDC/NIOSH) Sentinel Event Notification System 

for Occupational Risk-Pesticides (SENSOR) databases was consulted for pesticide incident data 

on the active ingredients metam sodium, metam potassium and MITC. Metam sodium, metam 

potassium and MITC are not included in the Agricultural Health Study (AHS) and therefore no

information from AHS was included in this report.

The IDS includes reports of alleged human health incidents from various sources, including 

mandatory Federal Insecticide, Fungicide and Rodenticide Act (FIFRA) Section 6 (a) (2) reports 

from registrants, other federal and state health and environmental agencies and individual 

consumers. IDS contain reports from across the U.S. and most incidents have all relevant 

product information recorded. Reports submitted to the IDS represent anecdotal reports or 

allegations only, unless otherwise stated in the report. IDS records incidents resulting in higher

severity outcomes in more detail, in a module called the Main IDS module. This system stores 

incident data for death, major and moderate incidents, and it includes more details about the 

location, date and nature of the incident.

In Aggregate IDS, from January 1, 2008 to February 19, 2013, there were eight reported

incidents involving metam sodium, one reported incident involving metam potassium, and three

reported incidents involving MITC. These incidents were classified as minor severity. For the 

Main IDS, from January 1, 2008 to February 19, 2013, there were five reported incidents 

involving metam sodium, one reported incident involving metam potassium, and one reported

incident involving MITC for the single chemicals only in the database. All of these incidents

were classified as moderate severity. There was one additional incident for metam sodium that 

was reported as involving more than one chemical.

The SENSOR-Pesticides database covers 11 states from 1998-2009, although reporting varies 

from state to state. Cases of pesticide-related illnesses are ascertained from a variety of sources, 

including: reports from local Poison Control Centers, state Department of Labor workers’ 

compensation claims when reported by physicians, reports from State Departments of 

Agriculture, and physician reports to state Departments of Health. Although both occupational 

and non-occupational incidents are included in the database, SENSOR-Pesticides focuses on 

occupational pesticide incidents, and is of particular value in providing that information. The 

state coordinator at the 11 respective state Departments of Health conducts case follow-up 

activities such as obtaining medical records to verify symptoms and severity. Using standardized 

protocol and case definitions derived from poison center reporting, the state SENSOR-Pesticide 

coordinator enters the incident information into the state-based system which is sent to NIOSH 

annually to be aggregated. 

A query of SENSOR-Pesticides 1998-2009 identifies 136 cases (stemming from 60 events) for 

metam sodium, 3 cases (stemming from 3 events) for metam potassium, and two cases 

(stemming from two events) for MITC. Almost all of these cases were involved a single active 
Metam Sodium/Metam Potassium/MITC Registration Review Human-Health Assessment Scoping Document

_____________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________ __________________________

Page 13 of 27

ingredient. Most of these cases were classified as low severity, some were moderate severity, 

and a few were high severity. 

Based on the number of incidents reported for these chemicals, the effects noted in the incidents,

and the recently implemented safety measures put into place in 2012 for all soil fumigant 

pesticides; metam sodium, metam potassium, and MITC warrant further incident analysis during 

Registration Review. This further analysis will include reviewing metam sodium, metam 

potassium, and MITC incident data from other sources as well as cases studies and a medical 

literature search on human health effects of metam sodium, metam potassium, and MITC.

9.0 Tolerance Assessment and International Harmonization

There are currently no tolerances for metam sodium, metam potassium, and MITC (see Section 

3.0 above).

 

10.0 Environmental Justice

Potential areas of environmental justice concerns, to the extent possible, were considered in the 

most recent metam sodium/potassium and MITC human-health risk assessment, in accordance 

with U.S. Executive Order 12898, “Federal Actions to Address Environmental Justice in 

Minority Populations and Low-Income Populations,” 

(http://www.hss.energy.gov/nuclearsafety/env/guidance/justice/eo12898.pdf). The OPP 

typically considers the highest potential exposures from the legal use of a pesticide when 

conducting human-health risk assessments, including, but not limited to, people who obtain 

drinking water from sources near agricultural areas, the variability of diets within the U.S., and 

people who may be exposed when harvesting crops. Should these highest exposures indicate 

potential risks of concern, OPP further refines the risk assessments to ensure that the risk 

estimates are based on the best available information.

11.0 Cumulative

Unlike other pesticides for which EPA has followed a cumulative risk approach based on a 

common mechanism of toxicity, EPA has not made a common mechanism of toxicity finding as 

to metam sodium, metam potassium, or MITC and any other substances. For the purposes of this 

assessment, therefore, EPA has not assumed that metam sodium, metam potassium, or MITC has 

a common mechanism of toxicity with other substances. For information regarding EPA’s efforts 

to determine which chemicals have a common mechanism of toxicity and to evaluate the 

cumulative effects of such chemicals, see the policy statements released by EPA’s Office of 

Pesticide Programs concerning common mechanism determinations and procedures for 

cumulating effects from substances found to have a common mechanism on EPA’s website at 

http://www.epa.gov/pesticides/cumulative/.

12.0 Endocrine Disruption

As required by the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) and the Federal 

Food, Drug, and Cosmetic Act (FFDCA), EPA reviews numerous studies to assess potential 

adverse outcomes from exposure to chemicals. Collectively, these studies include acute, 

subchronic and chronic toxicity, including assessments of carcinogenicity, neurotoxicity, 

developmental, reproductive, and general or systemic toxicity. These studies include endpoints 

which may be susceptible to endocrine influence, including effects on endocrine target organ 
Metam Sodium/Metam Potassium/MITC Registration Review Human-Health Assessment Scoping Document

_____________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________ __________________________

Page 14 of 27

histopathology, organ weights, estrus cyclicity, sexual maturation, fertility, pregnancy rates, 

reproductive loss, and sex ratios in offspring. For ecological hazard assessments, EPA evaluates 

acute tests and chronic studies that assess growth, developmental and reproductive effects in 

different taxonomic groups. As part of its most recent registration decision, EPA reviewed these 

data and selected the most sensitive endpoints for relevant risk assessment scenarios from the 

existing hazard database. However, as required by FFDCA section 408(p), prometryn is subject 

to the endocrine screening part of the Endocrine Disruptor Screening Program (EDSP). 

EPA has developed the EDSP to determine whether certain substances (including pesticide 

active and other ingredients) may have an effect in humans or wildlife similar to an effect 

produced by a “naturally occurring estrogen, or other such endocrine effects as the Administrator 

may designate.” The EDSP employs a two-tiered approach to making the statutorily required 

determinations. Tier 1 consists of a battery of 11 screening assays to identify the potential of a 

chemical substance to interact with the estrogen, androgen, or thyroid (E, A, or T) hormonal 

systems. Chemicals that go through Tier 1 screening and are found to have the potential to 

interact with E, A, or T hormonal systems will proceed to the next stage of the EDSP where EPA 

will determine which, if any, of the Tier 2 tests are necessary based on the available data. Tier 2 

testing is designed to identify any adverse endocrine-related effects caused by the substance, and 

establish a dose-response relationship between the dose and the E, A, or T effect. 

Under FFDCA section 408(p), the Agency must screen all pesticide chemicals. Between 

October 2009 and February 2010, EPA issued test orders/data call-ins for the first group of 67 

chemicals, which contains 58 pesticide active ingredients and 9 inert ingredients. Metam 

sodium, metam potassium, and MITC are not among the group of 58 pesticide active ingredients 

on the initial list to be screened under the EDSP. Accordingly, as part of Registration Review, 

EPA will issue future EDSP orders/data call-ins, requiring the submission of EDSP screening 

assays for prometryn. For further information on the status of the EDSP, the policies and 

procedures, the list of 67 chemicals, future lists, the test guidelines and the Tier 1 screening 

battery, please visit our website: http://www.epa.gov/endo/.

13.0 Human Studies

Past metam sodium/potassium and MITC risk assessments rely on an intentional dosing eye 

irritation and odor threshold study in human subjects (MRID no. 44400401) as the basis for the 

acute MITC endpoint. The Human Studies Review Board (HSRB) reviewed this study at a May 

2-3, 2006 meeting. The HSRB concluded that all applicable requirements of EPA’s Rule for the 

Protection of Human Subjects of Research (40 CFR Part 26) were satisfied in the study and that 

there was no regulatory barrier to continued reliance on these studies.

Past metam sodium/potassium and MITC risk assessments also rely in part on data from studies 

in which adult human subjects were intentionally exposed to a pesticide to determine their 

dermal and inhalation exposure. Many such studies, involving exposure to many different 

pesticides, comprise generic pesticide exposure databases such as PHED and the Outdoor 

Residential Exposure Task Force (ORETF) Database. EPA has reviewed all the studies 

supporting these multi-pesticide generic exposure databases, and has found no clear and 

convincing evidence that the conduct of any of them was either fundamentally unethical or 

significantly deficient relative to the ethical standards prevailing at the time the research was 

conducted. All applicable requirements of EPA’s Rule for the Protection of Human Subjects of 

Research (40 CFR Part 26) have been satisfied, and there is no regulatory barrier to continued 

reliance on these studies.
Metam Sodium/Metam Potassium/MITC Registration Review Human-Health Assessment Scoping Document

_____________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________ __________________________

Page 15 of 27

14.0 Risk Assessment Updates and Data Deficiencies

The occupational and residential exposure database for metam sodium, metam potassium, and 

MITC is adequate for Registration Review with the exception of an ambient air study measuring 

MITC from soil fumigant applications and a number of antimicrobial occupational handler and 

post-application exposure studies required in the 2009 Amended RED. The registrants have 

completed and submitted a field volatility study for center pivot applications (conventional soil 

fumigation use) and a sewer treatment occupational exposure study required for metam sodium 

as part of the 2009 Amended RED. In addition, the Agency requests that a shank injection 

tarped, bedded application flux study be completed. The Agency will review and incorporate all 

of these studies during Registration Review.

The Agency anticipates conducting the following risk assessment updates during Registration 

Review:

Toxicology: 

o Reevaluation of the toxicity endpoint/dose selection may be necessary based on 

the recently submitted toxicological data.

Residue Chemistry: None

Dietary Exposure: None

Occupational/Residential Exposure:

o Revised HED and AD occupational handler risk assessments may be necessary 

based on the most recent exposure data, Agency policies, or if the toxicological 

reevaluation results in changes to the endpoints.

o Revised AD occupational post-application risk assessments may be necessary 

based on the most recent exposure data, Agency policies, or if the toxicological 

reevaluation results in changes to the endpoints.

o Additional or revised HED residential bystander risk assessments may be 

necessary based on the most recent exposure data, Agency policies, or if the 

toxicological reevaluation of results in changes to the endpoints.

15.0 References

Memoranda Relevant to Registration Review.

Author Barcode Date Title

S. Kinard D293347 9/30/2003

Metam-sodium. Residue Chemistry Chapter for the 

Metam- sodium Reregistration Eligibility Decision 

(RED) Document.

T. Leighton and 

C. Walls D335651 2/14/2008

Metam Sodium: Revised Occupational and Residential 

Exposure Assessment of Antimicrobial Uses for the 

Reregistration Eligibility Decision Document. PC Code 

039003 (Metam Sodium) and 068103 (MITC).

C. Smith D357118 8/30/2009 Metam Sodium: Third Revision of the HED Human 

Health Risk Assessment.

J. Dawson, C. 

Smith, and S. 

Shelat

D385314 1/11/2011

Methyl Bromide (PC Code 053201), Chloropicrin (PC 

Code 081501), Dazomet (PC Code 035602), Metam 

Sodium and Potassium (PC Codes 039003 & 039002), 

MITC (PC Code 068103), DP Barcode 385314, Second 

Update To Health Effects Division Recommendations for 

Good Agricultural Practices and Associated Buffer 

Credits

S. Shelat D406930 2/26/2013 The Health Effects Division’s Review of the Metam Task 
Metam Sodium/Metam Potassium/MITC Registration Review Human-Health Assessment Scoping Document

_____________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________ __________________________

Page 16 of 27

Memoranda Relevant to Registration Review.

Author Barcode Date Title

Force Request for a Waiver for 2012 Methyl 

Isothiocyanate Ambient Air Monitoring Study (GDCI039003-840)

S. Recore and E. 

Evans D414492 08/29/2013 Metam Sodium, Metam Potassium, MITC: Review of Human Incidents

S. Shelat D406497 9/4/2013

Metam Sodium: Second Addendum to the Third Revision 

of the HED Human Health Risk Assessment and The 

Health Effects Division’s Review of the “Observational

Study to Determine Inhalation Exposure to Workers 

Treating Municipal Sewers Using SANAFORM 

VAPOROOTER II Foam Root Inhibitor” (dated 15 

August 2012)

Attachments: 

Attachment 1: Chemical Identity Table.

Attachment 2: Metam Sodium/Potassium and MITC Acute, Subchronic, and Chronic 

Toxicity Profile

Attachment 3: Metam Sodium/Potassium and MITC Endpoint Selection Tables.
Metam Sodium/Metam Potassium/MITC Registration Review Human-Health Assessment Scoping Document

_____________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________ __________________________

Page 17 of 27

Attachment 1: Chemical Identity Table.

Physical and Chemical Properties of Metam Sodium, Metam Potassium, and MITC 

Parameter Metam Sodium Metam Potassium MITC

Mode of Pesticidal Action generates MITC generates MITC The registrants have 

hypothesized that MITC 

interacts with a group of 

cation channels known as the 

transient receptor potential 

(TRP) family (see also 

Bandell, Story, Hwang, et al., 

2004). In particular the 

report suggests that TRPA1 

may be the target.

Appearance yellow to light yellow-green 

in solution

yellow to light yellow-green 

(aqueous formulation (54%)1)

colorless crystalline solid

Melting Point N/A N/A 35-36° C

Vapor Pressure 4.31 x 10-4 mm of Hg 24 mm of Hg at 25° C 

(aqueous formulation (54%)1)

20 mm of Hg at 25° C

Solubility in Water 578.29 g/L at 20° C yes, insoluble in mineral oil 8.94 g/L at 20° C

1 Data for the aqueous formulations MPs/EPs have been accepted because of the difficulties encountered in producing and 

maintaining aqueous solutions containing higher concentrations of active ingredient.
Metam Sodium/Metam Potassium/MITC Registration Review Human-Health Assessment Scoping Document

_____________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________ __________________________

Page 18 of 27

Attachment 2: Metam Sodium/Potassium and MITC Acute, Subchronic, and Chronic 

Toxicity Profile (as of May 2013)

Attachment 2A. Acute Toxicity Data on Metam Sodium/Metam Potassium

Guideline 

No. Study Type MRIDs # Results Toxicity Category

81-1 Acute Oral-Rat 41277002 LD50 =7 80 mg/kg (male rats)

 845 mg/kg (female rats) III

81-2 Acute Dermal-Rat 41277003 

41286005 LD50 = >2020 mg/kg III

81-3 Acute Inhalation-Rat 41277004 LC50 = 2.27 mg/L III

81-4 Primary Eye Irritation 41277005

No corneal/iris involvement; 

all irritation was absent by 7 

days; Slight irritation

III

81-5

Primary Skin 

Irritation-Rabbit 41277006

non-irritating to the skin of 

male rabbits IV

81-6 Dermal Sensitization 43457705 Positive for sensitization in guinea pigs

Attachment 2B. Acute Toxicity Data on MITC

Guideline

No. Study Type MRID #(S). Results Toxicity Category

81-1 Acute Oral-Rat 00162331 LD50 = 82 mg/kg 

 55 mg/kg II

81-2 Acute Dermal-Rat 00162330

42443501

LD50 = 136-436 mg/kg 

 181 mg/kg I

81-3 Acute Inhalation-Rat 45919410 LC50 = 0.54 mg/L II

81-4 Primary Eye Irritation 00162328 corrosion of the cornea and 

conjunctivae I

81-5 Primary Skin Irritation 00162329 all animals died within one 

hour I

81-6 Dermal Sensitization 459194101 positive for sensitization in guinea pig
Metam Sodium/Metam Potassium/MITC Registration Review Human-Health Assessment Scoping Document

_________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________ ___________________________________________________________________________________________________________________________________ ___________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________

Page 19 of 27

Attachment 2C. Subchronic, Chronic, and Other Toxicities on Metam Sodium/Metam Potassium and MITC

Guideline No./ Study 

Type

Metam Sodium/Metam Potassium MITC

MRID No. (year)/ 

Classification /Doses Results

MRID No. (year)/ Classification 

/Doses Results

870.3100

90-Day oral toxicity 

rodents (rat)

42117302 (1991)

Unacceptable/guideline

0, 0.018, 0.089, 0.443 mg/mL

M: 0, 1.7, 8.1, 26.9 mg/kg/day

F: 0, 2.5, 9.3, 30.6 mg/kg/day

NOAEL = 1.7M/ 2.5F mg/kg/day

LOAEL = 8.1M/9.3 F mg/kg/day 

based on hematology and decrease 

absolute

body weight.

Not available

870.3100

90-Day oral toxicity 

rodents (mouse)

42117301 (1991)

Unacceptable/guideline

0, 0.018, 0.088, 0.35, and 0.62 

mg/ml 

M: 0, 2.7, 11.7, 52.4, and 78.7 

mg/kg/day

F: 0, 3.6, 15.2, 55.4, and 83.8 

mg/kg/day

NOAEL = 0.018 mg/mL; 2.7M/3.6 

F mg/kg/day 

LOAEL = 0.088 mg/mL; 11.7 

M/15.2 F mg/kg/day based on 

urinary bladder lesions 

(eosinophilic granules, cystitits and 

mucosal hyperplasia) in both sexes 

and decrease in hematological 

parameters (hemoglobin, RBC, 

hematocrit) in female

Not available

870.3150

90-Day oral toxicity in 

nonrodents (dog)

42600001 (1992)

Unacceptable/guideline

0, 1, 5, and 10 mg/kg/day

NOAEL = < 1 mg/kg/day

LOAEL = 1 mg/kg/day based on 

increase in plasma ALT, AST, and 

alkaline phosphatase, as well as 

increase incidence of biliary duct 

proliferation with inflammatory 

cell infiltration. 

Not available

870.3200

21/28/30-Day dermal 

toxicity

41106204 (1979)

Unacceptable/guideline 

Methods unacceptable 00132815 (1983)

Unacceptable/guideline

0, 0, 120, 240, or 480 mg/kg/day

NOAEL < 120 mg/kg/day

LOAEL = 120 mg/kg/day based 

on decreased body weight gain 

and food intake. Severe necrosis 

and corrosion of the skin. 

870.3200

21/28/30-Day dermal 

toxicity

Not available 41221406 (1986)

Unacceptable/guideline

0, 1.0, 10.0, and 100 mg/kg/day

NOAEL = 1 mg/kg/day

LOAEL = 10 mg/kg/day based 

on decreased serum albumin and 

increased globulin values in 

addition to increased liver 

weights.

Irritation at all doses 
Metam Sodium/Metam Potassium/MITC Registration Review Human-Health Assessment Scoping Document

_________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________ ___________________________________________________________________________________________________________________________________ ___________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________

Page 20 of 27

Guideline No./ Study 

Type

Metam Sodium/Metam Potassium MITC

MRID No. (year)/ 

Classification /Doses Results

MRID No. (year)/ Classification 

/Doses Results

870.3250

90-Day dermal toxicity

Not available Not available

870.3465

28-Day inhalation 

toxicity

Not available 45314802 (1987)

Acceptable/guideline

0, 5.1, 19.9, 100 ug/L

Systemic

NOAEL = 5 mg/m3 (1.7 ppm). 

Systemic LOAEL = 19.9 

mg/m3,(6.8 ppm), based on 

clinical signs consistent with 

irritation in both sexes and 

increased neutrophilic 

polymorphonuclear 

granulocytes in the blood of 

males. 

Extrathoracic (ET) region

ET NOAEL = 19.9 mg/m3(6.8 

ppm)

ET LOAEL = 100 mg/m3,(34 

ppm), based on observation of 

pathological changes of the 

nasal cavity (metaplasia of 

respiratory epithelium and 

atrophy of the olfactory 

epithelium). 

Tracheabronchial (TB) region

TB NOAEL is 19.9 mg/m3(6.8 

ppm)

TB LOAEL = 100 mg/m3 (34 

ppm), based on observation of 

pathological changes (tracheal 

epithelial proliferation and 

single cell necrosis, 

bronchopneumonia and 

bronchial and bronchiolar 

epithelial proliferation). 
Metam Sodium/Metam Potassium/MITC Registration Review Human-Health Assessment Scoping Document

_________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________ ___________________________________________________________________________________________________________________________________ ___________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________

Page 21 of 27

Guideline No./ Study 

Type

Metam Sodium/Metam Potassium MITC

MRID No. (year)/ 

Classification /Doses Results

MRID No. (year)/ Classification 

/Doses Results

870.3465

90-Day inhalation 

toxicity

00162041 (1983)

Acceptable/guideline

0, 6.5, 45 and 160 mg/m3

NOAEL = 6.5 mg/m3; 1.11 

mg/kg/day

LOAEL = 45 mg/m3; 7.71 

mg/kg/day based on 

histopathological changes in the 

nasal passages (i.e., mucigenic 

hyperplasia) and changes in clinical 

chemistry.

41221407 (1978)

Acceptable/guideline

0, 3.16, 30.67, and 137.13 ug/L 

for 4 hours/day

0, 2.1, 20.6, and 91.9 ug/L 

extrapolated to 6 hour exposure

NOAEL = 3.16 ug/L

LOAEL = 30.67 ug/L based on 

decreased body weight, food 

efficiency and blood protein 

values accompanied by 

increased water intake. 

870.3465

90-Day inhalation 

toxicity (rats)

48869801 (2012)

Acceptable/guideline

0,1, 5, or 15 ppm

0, 3, 15, or 50 ug/L for 6 

hours/day

Portal of Entry

NOAEL = 3 ug/L

LOAEL = 15 ug/L based on 

lesions in the larynx and the 

nasal cavity.

Systemic

NOAEL = 50 ug/L , highest 

dose tested (HDT)

870.3465

90-Day inhalation 

toxicity (mice)

48869601 (2012)

Acceptable/guideline

0,1, 5, or 20 ppm

0, 3, 15, or 60 ug/L for 6 

hours/day

Portal of Entry

NOAEL = 3 ug/L

LOAEL = 15 ug/L based on 

lesions in the larynx, the trachea 

and the nasal cavity. 

Systemic

NOAEL = 15 ug/L 

LOAEL = 60 ug/L based on 

reduced body weights (M & F).

870.3700a

Prenatal developmental 

in rodents 

42983701 (1993)

Acceptable/guideline

0, 5, 20, or 60 mg/kg bw/day 

Maternal NOAEL = 5 mg/kg/day

LOAEL = 20 mg/kg/day based on 

reduced body weight gain and 

decreased food consumption. 

Developmental NOAEL =5 

mg/kg/day

LOAEL = 20 mg/kg/day based on 

the increased incidence of skeletal 

observations and the increase in 

total resorptions and 

resorptions/dam.

44733602 (1998)

Acceptable/guideline

0, 3, 10, or 30 mg/kg/day

Maternal NOAEL = 3 

mg/kg/day

LOAEL = 10 mg/kg/day based 

on salivation and decreased 

body weight gain. 

Developmental NOAEL =10

mg/kg/day

LOAEL = 30 mg/kg/day based 

on reduced fetal weight and an 

increased incidence of the 

skeletal variation of unossified 

sternebra(e).
Metam Sodium/Metam Potassium/MITC Registration Review Human-Health Assessment Scoping Document

_________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________ ___________________________________________________________________________________________________________________________________ ___________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________

Page 22 of 27

Guideline No./ Study 

Type

Metam Sodium/Metam Potassium MITC

MRID No. (year)/ 

Classification /Doses Results

MRID No. (year)/ Classification 

/Doses Results

870.3700a

Prenatal developmental 

in rodents

41577101 (1987)

Acceptable/guideline

0, 4.22, 16.88, and 50.64 

mg/kg/day 

Maternal NOAEL = 4.22 

mg/kg/day

LOAEL = 16.88 mg/kg/day based 

on reduced body weight gain and 

decreased food efficiency. 

Developmental NOAEL = 4.22 

mg/kg/day

LOAEL = 16.88 mg/kg/day based 

on the increased incidence in 

postimplantation loss and decrease 

in the % of live fetuses/dam.

45919417 (1987)

Unacceptable/guideline 

0, 3, 10, or 30 mg/kg/day

Maternal NOAEL = 10 

mg/kg/day

LOAEL = 30 mg/kg/day based 

on decreased body weight gain 

and food consumption. 

Developmental NOAEL =10 

mg/kg/day

LOAEL = 30 mg/kg/day based 

on higher number of runts and 

reduced placental weights.

870.3700b

Prenatal developmental 

in nonrodents (rabbits)

42963101 (1991)

Acceptable/guideline

0, 5, 20, and 60 mg/kg/day 

Maternal NOAEL = 5 mg/kg/day 

LOAEL = 20 mg/kg/day based on 

the reduced body weight gain, 

reduced food consumption and 

food efficiency. 

Developmental NOAEL = 5 

mg/kg/day

LOAEL = 20mg/kg/day based on 

the increased incidence of skeletal 

observations. 

45919418 (1986)

Unacceptable/guideline

0, 1, 3 or 10 mg/kg/day

Maternal tentative NOAEL = 3 

mg/kg/day

Tentative LOAEL = 10 

mg/kg/day based on reduced 

body weight gain and food 

consumption.

Developmental NOAEL =10 

mg/kg/day

LOAEL > 10 mg/kg/day

40330901 (1987)

Unacceptable/guideline

0, 4.22, 12.66, 42.2 mg/kg/day

Numerous deficiencies

870.3700a

Prenatal developmental 

in rodents (rats) 

inhalation

48779701 (2012)

Acceptable/guideline

0,1, 4, or 12 ppm

0, 3, 12, or 35 ug/L for 6 

hours/day

Maternal NOAEL = 12 ug/L 

LOAEL = 35 ug/L based on 

decreased body weight, body 

weight gain, corrected body 

weight gain, and food 

consumption.

Developmental NOAEL = ≥35 

ug/L (HDT)
Metam Sodium/Metam Potassium/MITC Registration Review Human-Health Assessment Scoping Document

_________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________ ___________________________________________________________________________________________________________________________________ ___________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________

Page 23 of 27

Guideline No./ Study 

Type

Metam Sodium/Metam Potassium MITC

MRID No. (year)/ 

Classification /Doses Results

MRID No. (year)/ Classification 

/Doses Results

870.3700b

Prenatal developmental 

in nonrodents (rabbits) 

inhalation

48779501 (2012)

Acceptable/guideline

0,1, 5, or 15 ppm

0, 3, 15, or 50 ug/L for 6 

hours/day

Maternal NOAEL = 15 ug/L 

LOAEL = 50 ug/L based on 

mortality, clinical signs 

associated with the respiratory 

tract, unkempt appearance, blue 

areas on the face, gross findings 

in the respiratory tract and 

stomach, decreased body weight 

gain, and decreased food 

consumption.

Developmental NOAEL = ≥50 

ug/L (HDT)

870.3800

Reproduction and 

fertility effects 

43136101 (1993)

Acceptable/ guideline

0, 0.01, 0.03, 0.1 mg/mL

M: 0, 1.2, 3.2, or 11.5 mg/kg/day

F: 0, 1.8, 3.9, or 13.5 mg/kg/day

Parental/Systemic NOAEL = 3.2 

M/ 3.9 F mg/kg/day

LOAEL = 11.5M/ 13.5F 

mg/kg/day based on pathology of 

Bowman’s gland duct and 

olfactory epithelium.

Reproductive NOAEL = 

11.5M/13.5F mg/kg/day

LOAEL =11.5M/13.5F 

mg/kg/day (HDT).

Offspring NOAEL = 3.2M/ 3.9 F 

mg/kg/day

LOAEL = 11.5M/ 13.5F 

mg/kg/day based on decrease pup 

weight.

40974601 (1987)

Unacceptable/guideline

0, 2, 10, and 50 ppm

M P: 0, 0.16, 0.76 and 3.58 

mg/kg/day

F P: 0, 0.21, 1.01, and 4.76 

mg/kg/day

M F1 0, 0.15, 0.71, 3.4 mg/kg/day

F F1: 0, 0.19, 0.87, 4.22 

mg/kg/day

Parental/Systemic NOAEL = 

10 ppm, 0.71 mg/kg/day 

LOAEL = 50 ppm, 3.4 

mg/kg/day based on decreased 

body weight gain in F1 males.

Reproductive NOAEL = 50 

ppm, 3.4M/ 4.22F mg/kg/day

LOAEL > 50 ppm, 3.4M/ 4.22F 

mg/kg/day

Offspring NOAEL = 50 ppm, 

3.4M/ 4.22F mg/kg/day 

LOAEL > 50 ppm, 3.4M/ 4.22F 

mg/kg/day

870.4100a

Chronic toxicity rodents

See combined chronic/carcinogenicity See combined chronic/carcinogenicity

870.4100b

Chronic toxicity dogs

43275801 (1994)

Acceptable/guideline

0, 0.05, 0.1, and 1.0 mg/kg/day 

NOAEL =1M/ 0.1F mg/kg/day

LOAEL >1 M/ 1 F mg/kg/day, 

based on increased ALT and 

microscopic changes in the liver in 

females.

41240701 (1988)

Unacceptable/guideline

0, 0.04, 0.4, 2.0 mg/kg/day

NOAEL = 0.4 mg/kg/day

LOAEL = 2.0 mg/kg/day based 

on excessive salivation, RBC 

measures, and increased liver 

weights.
Metam Sodium/Metam Potassium/MITC Registration Review Human-Health Assessment Scoping Document

_________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________ ___________________________________________________________________________________________________________________________________ ___________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________

Page 24 of 27

Guideline No./ Study 

Type

Metam Sodium/Metam Potassium MITC

MRID No. (year)/ 

Classification /Doses Results

MRID No. (year)/ Classification 

/Doses Results

870.4300

Combined Chronic/

Carcinogenicity rats

43275802 (1994)

Acceptable/guideline 

0, 0.019, 0.056, and 0.19 mg/mL 

M: 0, 1.3, 3.9, and 12.0 

mg/kg/day

F: 0, 2.3, 6.2, and 16.2 

mg/kg/day

NOAEL = 0.056 mg/mL 

LOAEL =0.19 mg/mL based on the 

changes in body weight gain, food 

efficiency, hematologic and clinical 

chemistry alterations, and macroand microscopic abnormalities 

observed at this dose in both sexes. 

00150078 (1984)

Unacceptable/guideline 

0, 2, 10, and 50 ppm 

0, 0.2, 1.0 and 5 mg/kg/day

NOAEL = 50 ppm

LOAEL = > 50 ppm 

870.4300

Chronic/Carcinogenicity 

mice

43233501 (1994)

Acceptable/guideline 

0, 0.019, 0.074, and 0.23 mg/mL 

M: 0, 1.6, 6.5, and 27.7 

mg/kg/day

F: 0, 2.3, 8.7 and 29.9 

mg/kg/day

NOAEL = 1.6 M/ 2.3 F mg/kg/day

LOAEL = 6.5 M/ 8.7F mg/kg/day 

based on significant increase in 

liver weight, and decrease body 

weight gain, food and water 

consumption in male and female 

mice. 

Evidence of carcinogenicity

00150075 (1980)

Unacceptable/guideline

0, 5, 20, 80, and 200 ppm

M: 0, 0.82, 3.30, 11.83, and 25.71 

mg/kg/day 

F: 0, 0.91, 3.66, 13.03, 29.03 

mg/kg/day

NOAEL = 20 ppm; 0.82 M/0.91 

F mg/kg/day

LOAEL = 80 ppm, 3.30 M/ 3.66 

F mg/kg/day based on decreased 

body weight gain throughout the 

majority of the study and 

reduced water consumption. 

870.5100 

Reverse Gene Mutation 

– Salmonella 

typhimurium

40305602 (1987)

Acceptable/guideline

0, 20, 100, 500, 1000, 1500, 

2000, and 2500 μg/plate +/-S9 

(standard plate test)

0, 4, 20, 100, 200, 300, 400, 

500, 1000, and 2500 μg/plate +/-

S9 (pre-incubation test)

Not mutagenic at any concentration 

+/-S9.

41221410 (1978)

Acceptable/Guideline

0, 0.5, 1, 5, 10, 50, 100, 500 and 

1000 μg/disc +/-S9

Negative in S. typhimurium and 

Escherichia coli WP2 uvrA up 

to severely cytotoxic 

concentrations (500 and 1000 

μg/disc +/-S9)

870.5375

Chromosome Aberration 

– mammalian cells 

40305604 (1987)

Acceptable/guideline

0, 1, 5, 10, and 20 μg/mL-S9; 0, 

10, 20 and 40 μg/mL+S9 

Positive in human lymphocytes –S9 

at concentrations causing severe 

cytotoxicity.

Positive +S9 at 20 and 40 μg/mL; 

predominant type of aberration = 

chromatid breaks

41221411 (1988)

Acceptable/guideline

0, 3.0 & 5.0 μg -/+S9

Negative in human lymphocytes 

up to a cytotoxic concentration 

(5.0 μg -/+S9)

870.5385

Mammalian bone 

marrow cytogenetic 

assay in Chinese 

hamsters 

40305605 (1987)

Acceptable/guideline

0, 150, 300, and 600 mg/kg

Negative Not available

870.5395

Micronucleus Assay –

Mice

Not available 48631101 (2011)

Acceptable/guideline

0, 20, 40, and 100 ppm 

(inhalation)

Negative up to a toxic 

concentration (100 ppm)
Metam Sodium/Metam Potassium/MITC Registration Review Human-Health Assessment Scoping Document

_________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________ ___________________________________________________________________________________________________________________________________ ___________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________

Page 25 of 27

Guideline No./ Study 

Type

Metam Sodium/Metam Potassium MITC

MRID No. (year)/ 

Classification /Doses Results

MRID No. (year)/ Classification 

/Doses Results

870.5500

Bacterial DNA damage 

or repair tests—Bacillus 

subtilis rec assay

40305602 (1987)

0, 0.1, 1.0, 5.0, 10.0, 25.0, 50.0, 

100.0, and 150.0 μL/plate +/-S9;

Preferential cytotoxicity not 

induced at any concentration

41221410 (1978)

Unacceptable

0, 20, 100, 200, 500, 1000, and 

2000 μg/disc –S9

Negative

870.5550

Unscheduled DNA 

Synthesis -Rat 

Hepatocytes

40305601 (1987)

Acceptable/guideline

0, 0.5, 1.0, 2.5, 5.0, 10.0, 50.0, 

100.0, and 250.0 nL/mL

Negative up to cytotoxic 

concentrations (100 nL/mL)

00150072 (1985)

Unacceptable

Negative up to 15.2 μg/mL

870.5900

In vitro sister chromatid 

exchange 

- Chinese hamster V79 

lung fibroblasts

Not available 41221412 (1988)

Acceptable/guideline

0, 0.1, 2.0 or 3.5 μg/mL –S9

0, 0.1, 2.5 or 5 μg/mL +S9

Negative up to the highest dose 

tested

870.6200a

Acute neurotoxicity 

screening battery

42977802 (1993)

Acceptable/guideline 

0, 22, 324, and 647 mg/kg 

NOAEL = < 22 mg/kg

LOAEL = 22 mg/kg based on 

reduced ambulatory and total 

motor activity observed in male 

and female rats on day 0, 45 

minutes post-dosing. 

Not available 

870.6200a

Acute neurotoxicity 

screening battery 

inhalation (rats)

Not available 48675701 (2011)

Acceptable/guideline 

0, 20, 40, or 80 ppm (0, 0.06, 

0.12, or 0.24 mg/L

Portal of Entry

LOAEL = 20 ppm (0.06 mg/L) 

based on mild to severe necrosis 

of the olfactory epithelium (1/6 

M; 5/6 F), which was not 

resolved in the 2-week exposure 

time.

Systemic/Neurotoxic

NOAEL = 20 ppm (0.06 mg/L) 

LOAEL = 40 ppm (0.12 mg/L, 

based on rales and gasping on 

study days 1 & 2 and decreased 

locomotor activity on study day 

0 in both sexes. 

870.6200b

Subchronic neurotoxicity 

screening battery

43248801 (1994)

Acceptable/guideline 

0, 0.02, 0.06,and 0.20 mg/mL 

M: 0, 1.4, 5.0, and 12.8 

mg/kg/day

F: 0, 2.3,7.0 and 15.5 mg/kg/day

NOAEL = 1.4 M/ 2.3F mg/kg/day

LOAEL = 5.0 M/ 7.0 F 

mg/kg/day based on decreased 

body weight gain for male and 

female rats. 

Not available 
Metam Sodium/Metam Potassium/MITC Registration Review Human-Health Assessment Scoping Document

_________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________ ___________________________________________________________________________________________________________________________________ ___________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________

Page 26 of 27

Guideline No./ Study 

Type

Metam Sodium/Metam Potassium MITC

MRID No. (year)/ 

Classification /Doses Results

MRID No. (year)/ Classification 

/Doses Results

870.6300

Developmental 

neurotoxicity

Not available Not available 

870.7600

Dermal penetration

42670301 (1992)

Acceptable/guideline 

0.1, 1, 10 mg/rat

Mean absorbed at 10 hours = 

2.52%

Not available 

870.7800

Immunotoxicity

28-day Inhalation

mice

Not required 148694901 (2011)

Acceptable/guideline

0, 1, 3 or 10 ppm

(0, 3, 9 or 30 μg/L 6 hrs/day for 

28 days

10 female mice/group

Systemic:

NOAEL = 10 ppm (highest dose 

tested).

LOAEL = Not established.

Immunotoxicity:

NOAEL = 10 ppm (highest dose 

tested).

LOAEL = >10 ppm

Special Study: Human 

Eye Irritation and Odor 

Threshold

Not available 44400401 (1996)

Acceptable/non-guideline

0, 0.22, 0.6, 0.8, 1.9, 3.3 ppm

One-minute exposure, the 

NOAEL for eye irritation is 3.3 

ppm due to a lack of response in 

any parameter tested. 

4-14 minutes, the NOAEL for 

eye irritation is 0.6 ppm based 

on responses on the Likert 

subjective scale at 1.9 ppm. 

1-8 hours, based on the 

statistically significant 

subjective (Likert scale) 

responses at 0.8 ppm MITC at 1-

4 hours and the statistically 

significant eyeblink responses at 

2 and 3 hours, 0.22 ppm was 

designated as the NOAEL for 

this study

1 HED’s Hazard and Science Policy Council (HASPOC) has determined that an Immunotoxicity study is not required for metam sodium/metam potassium (A. Dunbar; 5/22/13; 

TXR 0056665).
Metam Sodium/Metam Potassium/MITC Registration Review Human-Health Assessment Scoping Document

_________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________ ___________________________________________________________________________________________________________________________________ ___________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________

Page 27 of 27

Attachment 3: Metam Sodium/Potassium and MITC Endpoint from 2009 Risk 

Assessment.

Summary of Toxicological Dose and Endpoints for Use in Metam Sodium/Potassium

Occupational Dermal Human Health Risk Assessments

Exposure

Scenario Dose Used in Risk Assessment

Uncertainty Factors and 

Level of Concern for 

Risk Assessment

Study and Toxicological Effects

Dermal 

Short-Term 

(1 - 30 days)

Occupational

Maternal NOAELa,d = 4.22 

mg/kg/day

Dermal absorption factor = 2.5%

Occupational = LOC for 

MOE = 100 b,c

Developmental toxicity in rat (MRID 41577101)

LOAELe= 16.88 mg/kg/day based on reduced body 

weight gain and decreased food efficiency in 

maternal rats

Dermal 

Intermediate-Term 

(1 - 6 Months)

Occupational

Oral NOAELa,d = 0.1 mg/kg/day 

Dermal absorption factor = 2.5%

Occupational = LOC for 

MOE = 100 b,c

Chronic toxicity in dog (MRID 43275801)

LOAELe= 1 mg/kg/day based on increased ALT and 

microscopic changes in the liver in females. 

Cancer Classification: Probable human carcinogen (B2)

Q1* =1.98x10-1 in human equivalents converted from animals

a Since an oral NOAEL was selected, a dermal absorption factor of 2.5% should be used in route-to-route extrapolation.; b 

Margin of Exposure (MOE) = 100 [10x for interspecies extrapolation and 10x for intraspecies variations.]; c LOC = level of 

concern; d NOAEL = no observed adverse effect level; e LOAEL = lowest observed adverse effect level.

Summary of Toxicological Dose and Endpoints for Use in MITC Occupational and Residential 

Human Health Inhalation Risk Assessment

Risk Assessment Study NOAEL/LOAEL Endpoints HECsc

/HCs d

Acute

Non-occupational

and

Occupational

Eye irritation study 

(MRID 44400401)

One minute NOAELa

= 3.3 ppm

4-14 minutes 

NOAELa= 0.6 ppm

1-8 hours NOAELa= 

0.22 ppm 

Subjective responses to the 

Likert scale and eyeblink

responses

One minute HC = 3.3 ppm

UF = 10

4-14 minutes HC = 0.6 ppm

UF = 10

1-8 hours HC = 0.22 ppm 

UF = 10

Short- and 

IntermediateTerm Inhalation

(1 day to 6 

months)

Non-occupational

28-day inhalation 

study in rat

(MRID 43514802)

NOAELa= 6.8 ppm 

LOAELb= 34 ppm

Metaplasia of respiratory 

epithelium and atrophy of 

the olfactory epithelium

HEC = 0.16 ppm 

UF = 30

Occupational Same as non-occupational HEC = 0.68 ppm

UF = 30e

Long-Term 

Inhalation

(>6 months)

Non-occupational

28-day inhalation 

study in rat

(MRID 43514802)

NOAELa= 6.8 ppm 

LOAELb= 34 ppm

Metaplasia of respiratory 

epithelium and atrophy of 

the olfactory epithelium

HEC = 0.16 ppm 

UF = 300

Occupational Same as non-occupational HEC = 0.68 ppm

UF = 300 e

Cancer Classification: Insufficient data to characterize cancer risk

a NOAEL = no observed adverse effect level; b LOAEL = low observed adverse effect level; c HEC = Human equivalent 

concentration; d HC = Human concentration.; e HECs differ between non-occupational and occupational scenarios because the 

residential HEC is based on 24-hour exposures occurring 7 days per week, whereas the occupational HEC is based on 8-hour 

exposures occurring 5 days per week.